Oligogenic basis of premature ovarian insufficiency: an observational study

Panpan Long; Le Wang; Hangjing Tan; Ruping Quan; Zihao Hu; Minghua Zeng; Ziheng Deng; Hualin Huang; Jonathan Greenbaum; Hongwen Deng; Hongmei Xiao

doi:10.1186/s13048-024-01351-1

Oligogenic basis of premature ovarian insufficiency: an observational study

J Ovarian Res. 2024 Feb 3;17(1):32. doi: 10.1186/s13048-024-01351-1.

Authors

Panpan Long^#^{1

2}, Le Wang^#^{1

2

3}, Hangjing Tan^{1

2}, Ruping Quan^{1

2}, Zihao Hu^{1

2}, Minghua Zeng^{1

2}, Ziheng Deng^{1

2}, Hualin Huang⁴, Jonathan Greenbaum⁵, Hongwen Deng⁵, Hongmei Xiao^{6

7}

Affiliations

¹ Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, 88 Xiangya Road, Changsha, 410008, Hunan, China.
² Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, China.
³ Biomedical Research Center, Hunan University of Medicine, Huaihua, China.
⁴ Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, China.
⁵ Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
⁶ Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, 88 Xiangya Road, Changsha, 410008, Hunan, China. hmxiao@csu.edu.cn.
⁷ Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, China. hmxiao@csu.edu.cn.

^# Contributed equally.

Abstract

Background: The etiology of premature ovarian insufficiency, that is, the loss of ovarian activity before 40 years of age, is complex. Studies suggest that genetic factors are involved in 20-25% of cases. The aim of this study was to explore the oligogenic basis of premature ovarian insufficiency.

Results: Whole-exome sequencing of 93 patients with POI and whole-genome sequencing of 465 controls were performed. In the gene-burden analysis, multiple genetic variants, including those associated with DNA damage repair and meiosis, were more common in participants with premature ovarian insufficiency than in controls. The ORVAL-platform analysis confirmed the pathogenicity of the RAD52 and MSH6 combination.

Conclusions: The results of this study indicate that oligogenic inheritance is an important cause of premature ovarian insufficiency and provide insights into the biological mechanisms underlying premature ovarian insufficiency.

Keywords: Gene-burden analysis; ORVAL platform; Oligogenic inheritance; Premature ovarian insufficiency; Whole-exome sequencing.

Publication types

Observational Study

MeSH terms

Female
Humans
Menopause, Premature* / genetics
Primary Ovarian Insufficiency* / genetics

Grants and funding

2017YFC1001100/National Key Research and Development Program of China